A number of monoclonal antibodies (mAb) have been derived from the immunization of mice with human gastrointestinal tumor cell lines (Koprowski, et al., (1979), Somat. Cell Genet. vol. 5, pp. 957-972; Steplewski, et al., (1982) in Methods in Cancer Research, eds. Busch, et al., (Academic, New York), vol. XX, pp. 285-316; Herlyn, et al., (1984), J. Immunol. Meth., vol. 73, pp. 157-167; Gottlinger, et al., (1986), Int. J. Cancer, vol. 38, pp. 47-53; Girardet, et al., (1986), J. Immunol., vol. 136, pp. 1497-1503). Investigations into the antigenic structures recognized by these mAb have identified a group of glycolipid and glycoprotein antigens (Steplewski, et al., (1982) in Methods in Cancer Research, eds. Busch, et al., (Academic, New York), vol. XX, pp. 285-316). The 40 kDa cell surface glycoprotein (Ross, et al., (1986), Hybridoma, vol. 5, pp. S21-S27) recognized by mAb CO17-1A (Herlyn, et al., (1986), Hybridoma, vol. 5, pp. S3-S8), and several other independently derived mAb (Gottlinger, et al., (1986), Int. J. Cancer, vol. 38, pp. 47-53; Girardet, et al., (1986), J. Immunol., vol. 136, pp. 1497-1503; Ross, et al., (1986), Biochem. Biophys. Res. Comm., vol. 135, pp. 297-303), is one of the most well-characterized tumor-associated antigens. Another cell surface glycoprotein antigen, defined by mAb CO-029 (formerly called 1116NS-29) (Koprowski, et al., (1979), Somat. Cell Genet. vol. 5, pp. 957-972), has been shown to be a .about.32 kDa monomer (Sela, et al., (1989), Hybridoma, vol. 8, pp. 481-491). The CO-029 antigen was found to be expressed on gastric, colon, rectal, and pancreatic carcinomas, but not on most normal tissues (Sela, et al., (1989), Hybridoma, vol. 8, pp. 481-491). MAb CO-029 has been shown to mediate antibody-dependent cell-mediated cytotoxicity in vitro (Koprowski, et al., (1979), Somat. Cell Genet. vol. 5, pp. 957-972). However, the CO-029 antigen has not been structurally characterized, nor has its coding sequence been isolated.
The recent molecular cloning of cDNA for tumor-associated antigens has provided information about antigen structure and the evolution of the genes encoding these antigens. cDNA clones have been isolated (Szala, et al., (1990), Proc. Natl. Acad. Sci. U.S.A., vol. 87, pp. 3542-3546) for the GA733-2 carcinoma-associated antigen defined by mAB GA733 (Herlyn, et al., (1986), Hybridoma, vol. 5, pp. S21-S27). Transfection experiments with a GA733-2 cDNA clone have shown that it encodes both the GA733 and CO17-1A epitopes (Szala, et al., (1990), Proc. Natl. Acad. Sci. U.S.A., vol. 87, pp. 3542-3546). Sequence analysis of GA733-2 found it to be identical with the mAb defined, tumor-associated antigen KSA (Strand, et al., (1989), Cancer Res., vol. 49, pp. 314-317). A related gene, GA733-1, has been identified and was found to have a 50% amino acid sequence homology with the GA733-2 antigen (Szala, et al., (1990), Proc. Natl. Acad. Sci. U.S.A., vol. 87, pp. 3542-3546; Linnenbach, et al., (1989), Proc. Natl. Acad. Sci. U.S.A., vol. 86, pp. 27-31). GA733-1 is an intronless gene that was shown to be transcribed at high levels in pancreatic carcinoma cell lines (Linnenbach, et al., (1989), Proc. Natl. Acad. Sci. U.S.A., vol. 86, pp. 27-31). The GA733 family of antigens are type I transmembrane proteins of unknown function.
There is a need in the art for additional cloned tumor-associated antigens. The clones can be used to determine nucleic acid sequences as well as to produce preparations of antigens which may be useful as vaccines to stimulate anti-tumor antibody production in cancer patients.